Device for sequential collection and sweat detection

Abstract

The invention provides a device capable of collecting and detecting a liquid sample in a time sequence, which comprises a noninvasive liquid sample collecting and sensing detection module, the non-invasive liquid sample collection and sensing detection module comprises a liquid sample flow channel in a Tesla valve form, a liquid sample inlet communicated with an inlet of a reverse channel of the liquid sample flow channel, and a liquid sample outlet communicated with an outlet of the reverse channel of the liquid sample flow channel; the liquid storage cavities are respectively communicated with each curve section of the liquid sample flow channel in the Tesla valve form, and electrodes of the electrochemical sensor are arranged close to the bottom ends of the liquid storage cavities. According to the device capable of collecting and detecting the liquid samples in the time sequence, the liquid storage cavities connected to the Tesla valve in series can effectively prevent liquid from flowing reversely through the design of the structure and the length, sweat detection of different time sequences can be achieved through the characteristic that the reverse flowing speed of the Tesla valve is low, and data changes of sweat are analyzed.

Description

Technical Field

[0001] The present invention relates to the fields of micro-electromechanical processing technology and microfluidic analysis and detection technology, and in particular to a device capable of sequentially collecting and detecting liquid samples. Background Art

[0002] Wearable sensor technology is crucial to improving the efficiency of human-device integration by continuously monitoring the user's work ability and health status and formulating scientific and personalized training plans. Sweat is an important biological fluid that contains rich biochemical substances, such as electrolytes (sodium, potassium, calcium, chloride, etc.), nitrogen-containing compounds (such as urea, amino acids, etc.), metabolites (such as glucose, lactic acid, uric acid, etc.) and hormones (such as cortisol, etc.), which contain rich physiological information. At the same time, the surface of human skin is densely covered with sweat glands, and sweat is very easy to obtain. The development of wearable non-invasive sweat sampling and analysis technology makes it easier to achieve non-invasive and non-invasive detection.

[0003] In 2016, researchers at the University of California, Berkeley, integrated a multi-channel electrochemical sensor to monitor glucose, lactate, sodium, potassium and temperature during exercise. At the same time, the Nanoparticle Research Center of the Institute of Basic Science in Seoul, South Korea, combined graphene with a gold grid for wearable sweat monitoring for diabetics. The main monitoring parameters include glucose, pH, humidity, and microneedles can be used to provide certain feedback treatment. The University of Texas at Dallas uses room temperature ionic liquids to detect interleukin 6 and cortisol in sweat. The content of interleukin 6 in human sweat is roughly consistent with that in blood. The sensor can detect interleukin 6 in sweat within 48 hours after functionalization. The School of Materials at the University of Illinois in the United States achieves the purpose of real-time monitoring of markers such as chloride ions, hydronium ions, glucose and lactate in sweat by designing and integrating colorimetric modules. Northwestern University also uses smartphones and fluorescent colorimetry to measure the concentrations of fluoride, sodium and zinc in sweat, achieving rapid quantitative analysis. Since the sample volume of sweat is relatively small, the collection is difficult and complicated, and it is easy to evaporate, the current sweat collection and detection is usually disposable, and can only detect single-point sweat. The present invention relates to a method for time-series collection and detection of sweat, which can obtain more sweat information, help analyze the change trend of sweat, and is of great significance to the accuracy of sweat data.

[0004] Tesla valve is a passive one-way valve structure first proposed by Tesla. Its characteristic is that it increases the resistance of reverse flow without interfering with the forward fluid. Specifically, the Tesla valve has little effect on the forward fluid, and the pressure on the negative fluid is several hundred times that of the forward fluid. The Tesla valve combines the capillary principle and describes the phenomenon of liquid rising in a thin tubular structure. Due to the mutual attraction between liquid molecules, the liquid will rise inside the thin tube until the tension generated by the surface tension of the liquid is balanced with the gravity of the liquid column in the tube. Summary of the invention

[0005] The purpose of the present invention is to provide a device capable of sequentially collecting and detecting liquid samples, which performs sequential collection and detection according to the liquid samples of users, has a simple structure, low cost and broad application prospects.

[0006] In order to achieve the above-mentioned objectives, the present invention provides a device capable of sequentially collecting and detecting liquid samples, which includes a non-invasive liquid sample collection and sensing detection module, wherein the non-invasive liquid sample collection and sensing detection module includes a liquid sample flow channel in the form of a Tesla valve, a liquid sample inlet connected to the inlet of a reverse channel of the liquid sample flow channel, a liquid sample outlet connected to the outlet of the reverse channel of the liquid sample flow channel, a plurality of liquid storage chambers respectively connected to each curved segment of the liquid sample flow channel in the form of a Tesla valve, and an electrochemical sensor, wherein the electrodes of the electrochemical sensor are arranged near the bottom end of each liquid storage chamber.

[0007] The liquid sample flow channel comprises a linear main flow channel and two liquid sample flow channels in the form of Tesla valves arranged on both sides of the main flow channel and in opposite directions.

[0008] The liquid sample flow channel has a Tesla valve structure unit, and the liquid storage chamber is arranged on the curve segment of each Tesla valve structure unit of the liquid sample flow channel in the form of a Tesla valve; and / or the number of Tesla valve structure units of the liquid sample flow channel and / or the volume of the liquid storage chamber are set according to the requirements of detection time and number of detections.

[0009] The non-invasive liquid sample collection and sensing detection module includes a skin adhesion layer, a flexible sensing layer and a microfluidic chip layer stacked in sequence from bottom to top; the liquid sample flow channel is formed by the groove structure provided on the side of the microfluidic chip layer facing the flexible sensing layer and the flexible sensing layer; the liquid sample inlet is defined by the first through hole penetrating the skin adhesion layer and the flexible sensing layer and the part of the microfluidic chip layer with the groove structure aligned with the first through hole; the liquid sample outlet is defined by the second through hole penetrating the microfluidic chip layer and communicating with the liquid sample flow channel and the flexible sensing layer; the liquid storage chamber is defined by the blind hole provided on the side of the microfluidic chip layer facing the flexible sensing layer and communicating with each curved segment of the liquid sample flow channel, the through hole or blind hole provided on the flexible sensing layer and aligned with the blind hole, and the skin adhesion layer.

[0010] The electrode of the electrochemical sensor is arranged on the surface of the flexible sensing layer facing the microfluidic chip layer, and one end is communicated with the liquid storage cavity.

[0011] The electrodes corresponding to each liquid storage cavity include a reference electrode, a counter electrode and a detection electrode. The detection electrode is modified according to the detection target and is used for specific detection of biomarkers.

[0012] The electrochemical sensor further includes a serial port connected to a plurality of electrodes of the electrochemical sensor at the same time.

[0013] The serial port is connected to a signal processing module to transmit the electrical signal detected by the electrode to the signal processing module.

[0014] The liquid sample includes body fluid of an animal or a plant.

[0015] The device capable of sequentially collecting and detecting liquid samples of the present invention combines microfluidic technology and electrochemical detection technology, improves the structure of the Tesla valve, and effectively prevents the reverse flow of liquid through the design of structure and length of multiple liquid storage chambers connected in series to the Tesla valve. The slow reverse flow characteristic of the Tesla valve can be used to achieve sweat detection at different time sequences and analyze the data changes of sweat. In other words, this design can not only reduce the interference of sweat gravity on the flow direction of sweat and reduce sweat reflux crosstalk, but also achieve the purpose of time-sharing detection, thereby obtaining more biological information.

[0016] Compared with the prior art, the device capable of sequentially collecting and detecting liquid samples of the present invention has a simple and reasonable structure, can prolong the storage time of sweat and reduce evaporation; multiple liquid storage chambers are added to the Tesla valve structure, which can separate sweat at different times, and detect and compare sweat data at different times, thereby reducing detection errors caused by individual differences. In addition, the number of Tesla valve structure units and / or the volume of the liquid storage chamber can be changed to be suitable for long-term and short-term sweat collection and detection. Different numbers of Tesla valve units can be designed according to needs, and the time interval of time-sharing detection can be changed, showing extremely high flexibility. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 It is an exploded schematic diagram of a non-invasive liquid sample collection and sensing detection module of a device capable of sequentially collecting and detecting liquid samples according to an embodiment of the present invention.

[0018] Figure 2 and Figure 3 This is a schematic diagram of the positive and negative flow of the Tesla valve structure. Figure 2 shows the case of forward flow, Figure 3 The reverse flow situation is shown.

[0019] Figure 4 It is a schematic diagram of the structure of a microfluidic chip layer of a device capable of sequentially collecting and detecting liquid samples.

[0020] Figure 5-Figure 8 This is a simulation diagram of the flow of sweat filled in the liquid storage chamber of the sweat sequential collection device. Figure 5 It shows that T 0 The situation at the moment; Figure 6 It shows that T 0 +40min time situation; Figure 7 It shows that T 0 +80min time situation; Figure 8 It shows that T 0 +120min time situation.

[0021] Reference numerals:

[0022] 10: liquid sample flow channel; 20: liquid sample inlet; 30: liquid sample outlet; 40: liquid storage chamber; 21: electrode; 22: detection serial port; 50: skin adhesion layer; 60: flexible sensing layer; 70: microfluidic chip layer 70. DETAILED DESCRIPTION

[0023] The present invention is described below in conjunction with the accompanying drawings.

[0024] The device capable of sequentially collecting and detecting liquid samples of the present invention comprises a non-invasive liquid sample collection and sensing detection module and a signal processing module. The device capable of sequentially collecting and detecting liquid samples of the present invention comprises a wearable body, and the non-invasive liquid sample collection and sensing detection module is installed on a side of the wearable body facing the detection object, so that the device capable of sequentially collecting and detecting liquid samples of the present invention is a wearable device as a whole.

[0025] Among them, the overall structure of the non-invasive liquid sample collection and sensor detection module is as follows Figure 1 As shown, it includes a liquid sample flow channel 10 in the form of a Tesla valve, a liquid sample inlet 20 connected to the inlet of the reverse channel of the liquid sample flow channel 10, a liquid sample outlet 30 connected to the outlet of the reverse channel of the liquid sample flow channel 10, and a plurality of liquid storage chambers 40 respectively connected to each curved segment of the liquid sample flow channel 10 in the form of a Tesla valve.

[0026] like Figure 4 As shown, in this embodiment, the liquid sample flow channel 10 includes a straight main channel and two liquid sample flow channels in the form of Tesla valves arranged on both sides of the main channel in opposite directions.

[0027] In this embodiment, the liquid sample is not limited to sweat, but can also be other trace liquids such as cerebrospinal fluid or pus; in addition, the device can also be used for body fluids of animals or plants, for example, for the detection of trace liquid components of plants, and can be used for the detection of other non-biological trace samples.

[0028] like Figure 2 As shown, the Tesla valve has very little resistance to the liquid sample from the liquid sample outlet 30 to the liquid sample inlet 20, and the liquid storage chamber 40 connected in series to the flow channel in the Tesla valve does not interfere with the forward flow. Figure 3 As shown, the Tesla valve has a large resistance to the liquid sample from the liquid sample inlet 20 to the liquid sample outlet 30, which prolongs the time for the liquid to fill the Tesla valve, thereby prolonging the time required for the liquid to flow in reverse, wherein the liquid storage chamber 40 can enhance the interference with the reverse fluid, and the reverse fluid will preferentially enter the liquid storage chamber 40 during the flow. Therefore, the Tesla valve can effectively prevent the reverse flow of liquid through the design of structure and length, and the slow speed of the reverse flow of the Tesla valve can be used to enable multiple liquid storage chambers 40 connected in series to the Tesla valve to achieve sweat detection at different time sequences. In the present invention, the reverse mentioned refers to Figure 3 Flow direction shown.

[0029] Because Figure 2The resistance of the Tesla valve to the reverse flow of liquid is shown, and the sweat will flow into the liquid storage chamber 40 of each Tesla valve structural unit in turn, realizing sweat detection at different times. The liquid storage chamber 40 is arranged on the curve segment of each Tesla valve structural unit of the liquid sample flow channel in the form of a Tesla valve. Preferably, if it is necessary to extend the detection time and the number of detections, the number of Tesla valve structural units can be increased according to the requirements of the detection time and the number of detections, or the volume of the liquid storage chamber 40 can be increased. Among them, by changing the volume of the liquid storage chamber 40, the volume required for sweat to fill the liquid storage chamber 40 can be changed, and the sweat detection time of the two liquid storage chambers 40 can be extended or shortened.

[0030] See also Figure 1 The non-invasive liquid sample collection and sensing detection module includes a skin adhesive layer 50, a flexible sensing layer 60 and a microfluidic chip layer 70 stacked in sequence from bottom to top. The skin adhesive layer 50 ensures that the device capable of sequentially collecting and detecting liquid samples of the present invention can stably adhere to the surface of human skin.

[0031] The liquid sample flow channel 10 is defined by the groove structure provided on the side of the microfluidic chip layer 70 facing the flexible sensing layer 60 and the flexible sensing layer 60. The liquid sample inlet 20 is defined by the first through hole penetrating the skin adhesive layer 50 and the flexible sensing layer 60 and the part of the microfluidic chip layer 70 with the groove structure aligned with the first through hole. The liquid sample outlet 30 is defined by the second through hole penetrating the microfluidic chip layer 70 and communicating with the liquid sample flow channel 10 and the flexible sensing layer 60. The liquid storage chamber 40 is defined by the blind hole provided on the side of the microfluidic chip layer 70 facing the flexible sensing layer 60 and communicating with each curved segment of the liquid sample flow channel 10, the through hole or blind hole provided on the flexible sensing layer 60 and aligned with the blind hole, and the skin adhesive layer 50.

[0032] The non-invasive liquid sample collection and sensing detection module further includes an electrochemical sensor, which includes a plurality of electrodes 21 disposed on the surface of the flexible sensing layer 60 facing the microfluidic chip layer 70 and connected to the liquid storage chamber 40 at one end, and a serial port 22 simultaneously connected to the plurality of electrodes 21. The serial port 22 is connected to the signal processing module to transmit the electrical signal detected by the electrode 21 to the signal processing module, so as to facilitate subsequent signal processing and display of the electrical signal.

[0033] The electrode 21 corresponding to each liquid storage cavity 40 includes a reference electrode, a counter electrode and a detection electrode. The potential of the reference electrode hardly changes during measurement. The counter electrode is used to form a current path with the working electrode. The detection electrode is modified according to the detection target and is used to specifically detect biomarkers. Thus, the electrode 21 and the serial port 22 are made into an electrochemical sensing unit of a biosensor that can specifically detect the corresponding biomarker. Due to the capillary principle, it is less affected by external forces, but in order to prevent the sensor from detecting in advance due to a small amount of sweat entering due to special circumstances such as severe shaking, the electrode 21 of each electrochemical sensor is placed close to the bottom of each liquid storage cavity 40.

[0034] When sweat flows into each liquid storage cavity 40, the components to be detected in the sweat combine with the modified detection electrode to generate an electrical signal. The biosensor continuously monitors at a certain frequency according to demand. During the process of continuous monitoring of the biosensor at a certain frequency, the liquid sample flow channel 10 in the form of a Tesla valve can extend the interval time of the electrochemical reaction in the adjacent detection cavity, thereby realizing the detection of sweat components at different time sequences. Compared with the current wearable sweat detection equipment, more sweat component information can be obtained.

[0035] Combine the following Figure 1 , Figure 5-Figure 8 The working principle of the device capable of sequentially collecting and detecting liquid samples of the present invention is described.

[0036] Specifically, after the sweat appears on the skin surface, it enters the microfluidic chip layer through the liquid sample inlet 20, and flows through the main channel of the liquid sample flow channel 10 to the liquid sample flow channels in the form of Tesla valves on both sides. At this time, the liquid sample flows in the liquid sample flow channels in the form of Tesla valves on both sides in a reverse direction (such as Figure 3 In the direction shown in the figure, the sweat will slowly fill up the chambers of the Tesla valves in sequence under the high pressure of the Tesla valve on the reverse fluid, and after entering the liquid storage chamber 40, it will symmetrically fill up the liquid storage chambers 40 connected in series to the curve section of the Tesla valve in sequence, and finally flow out through the liquid sample outlet 30 of the microfluidic chip layer. The detection electrode in the electrode 21 reacts to the components of the sweat in each chamber, and is connected to the signal processing module through the serial port 22 for signal processing and display.

[0037] Due to the presence of the liquid storage chamber 40, the sweat reverses during the flow (such as Figure 3 The flow shown in FIG. 4A will first fill the liquid storage chamber 40 near the Tesla valve outlet, as shown in FIG. Figure 5-Figure 8 As shown in the figure, the white part is sweat, the gray part is air, the right side is the liquid sample inlet 20, and the left side is the liquid sample outlet 30. Figure 5-Figure 8The figure shows the distribution of sweat at different times. It can be seen that the sweat fills up the three liquid storage chambers 40 in sequence, and there is a difference in the time when the sweat fills up the different liquid storage chambers 40. Therefore, the electrochemical sensors in the different liquid storage chambers 40 can detect the components of the sweat at different times and perform comparative analysis on the sweat at different times.

[0038] The device capable of sequentially collecting and detecting liquid samples of the present invention combines microfluidics and electrochemical detection technologies, improves the structure of the Tesla valve, and the multiple liquid storage chambers connected in series to the Tesla valve can effectively prevent the reverse flow of liquid through the design of structure and length. The slow reverse flow of the Tesla valve can be used to detect sweat at different time sequences and analyze the data changes of sweat. In other words, this design can not only reduce the interference of sweat gravity on the flow direction of sweat and reduce sweat reflux crosstalk, but also achieve the purpose of time-sharing detection, thereby obtaining more biological information.

[0039] Compared with the prior art, the device capable of sequentially collecting and detecting liquid samples of the present invention has a simple and reasonable structure, can prolong the storage time of sweat and reduce evaporation; multiple liquid storage chambers are added to the Tesla valve structure, which can separate sweat at different times, and detect and compare sweat data at different times, thereby reducing detection errors caused by individual differences. In addition, the number of Tesla valve structure units and / or the volume of the liquid storage chamber can be changed to be suitable for long-term and short-term sweat collection and detection. Different numbers of Tesla valve units can be designed according to needs, and the time interval of time-sharing detection can be changed, showing extremely high flexibility.

[0040] The above description is only for illustrating the implementation mode of the present invention and is not intended to limit the present invention. For those skilled in the art, any modification, equivalent substitution, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A device capable of sequentially collecting and detecting liquid samples, characterized in that: It includes a non-invasive liquid sample collection and sensing detection module, which includes a liquid sample flow channel in the form of a Tesla valve, a liquid sample inlet connected to the inlet of the reverse channel of the liquid sample flow channel, a liquid sample outlet connected to the outlet of the reverse channel of the liquid sample flow channel, a plurality of liquid storage chambers respectively connected to each curved segment of the liquid sample flow channel in the form of a Tesla valve, and an electrochemical sensor, wherein the electrode of the electrochemical sensor is arranged near the bottom end of each liquid storage chamber.

2. The device capable of sequentially collecting and detecting liquid samples according to claim 1, characterized in that: The liquid sample flow channel comprises a linear main flow channel and two liquid sample flow channels in the form of Tesla valves arranged on both sides of the main flow channel and in opposite directions.

3. The device capable of sequentially collecting and detecting liquid samples according to claim 1, characterized in that: The liquid sample flow channel has a Tesla valve structure unit, and the liquid storage chamber is arranged on a curve segment of each Tesla valve structure unit of the liquid sample flow channel in the form of a Tesla valve; and / or The number of Tesla valve structural units of the liquid sample flow channel and / or the volume of the liquid storage cavity are set according to the requirements of the detection time and the number of detection times.

4. The device capable of sequentially collecting and detecting liquid samples according to claim 1, characterized in that: The non-invasive liquid sample collection and sensing detection module comprises a skin adhesion layer, a flexible sensing layer and a microfluidic chip layer stacked in sequence from bottom to top; The liquid sample flow channel is formed by the groove structure provided on the side of the microfluidic chip layer facing the flexible sensing layer and the flexible sensing layer; the liquid sample inlet is defined by the first through hole penetrating the skin adhesion layer and the flexible sensing layer and the part of the microfluidic chip layer with the groove structure aligned with the first through hole; the liquid sample outlet is defined by the second through hole penetrating the microfluidic chip layer and communicating with the liquid sample flow channel and the flexible sensing layer; the liquid storage chamber is defined by the blind hole provided on the side of the microfluidic chip layer facing the flexible sensing layer and communicating with each curved segment of the liquid sample flow channel, the through hole or blind hole provided on the flexible sensing layer and aligned with the blind hole, and the skin adhesion layer.

5. The device capable of sequentially collecting and detecting liquid samples according to claim 4, characterized in that: The electrode of the electrochemical sensor is arranged on the surface of the flexible sensing layer facing the microfluidic chip layer, and one end is communicated with the liquid storage cavity.

6. The device capable of sequentially collecting and detecting liquid samples according to claim 1, characterized in that: The electrodes corresponding to each liquid storage cavity include a reference electrode, a counter electrode and a detection electrode. The detection electrode is modified according to the detection target and is used for specific detection of biomarkers.

7. The device capable of sequentially collecting and detecting liquid samples according to claim 1, characterized in that: The electrochemical sensor further includes a serial port connected to a plurality of electrodes of the electrochemical sensor at the same time.

8. The device capable of sequentially collecting and detecting liquid samples according to claim 7, characterized in that: The serial port is connected to a signal processing module to transmit the electrical signal detected by the electrode to the signal processing module.

9. The device capable of sequentially collecting and detecting liquid samples according to claim 1, characterized in that: The liquid sample includes body fluid of an animal or a plant.

10. The device capable of sequentially collecting and detecting liquid samples according to claim 1, characterized in that: It also includes a wearable body, and the non-invasive liquid sample collection and sensor detection module is installed on a side of the wearable body facing the detection object.

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